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A Novel Flp Reporter Mouse Shows That TRPA1 Expression Is Largely Limited to Sensory Neuron Subsets
Mayur J Patil1, Seol-Hee Kim1, Parmvir K Bahia1
1Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612.
Eneuro
|November 21, 2023
Summary
A new mouse model allows researchers to track cells expressing Transient Receptor Potential Ankyrin 1 (TRPA1). This tool helps map TRPA1 cells and understand their role in various bodily functions and diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Physiology
Background:
- Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel involved in sensory perception.
- TRPA1 is primarily found in nociceptive sensory neurons but also in other cell types.
- Understanding TRPA1 expression is crucial for developing new analgesics and studying various physiological processes.
Purpose of the Study:
- To develop a novel knock-in mouse model for visualizing and manipulating TRPA1-expressing cells.
- To validate the expression patterns of TRPA1 in different tissues and cell types using the new mouse model.
- To explore the potential applications of this mouse model in studying TRPA1's role in physiological and pathophysiological conditions.
Main Methods:
- Development of a TRPA1-FlpO knock-in mouse line.
- Crossing with a reporter mouse (R26) to achieve Flp-dependent tdTomato expression.
- Analysis of tdTomato expression in various tissues and correlation with TRPA1 mRNA and agonist sensitivity.
- Chemogenetic activation of TRPA1-expressing nerves to assess functional responses.
Main Results:
- The TRPA1-FlpO mouse successfully visualized TRPA1-expressing cells, particularly in vagal and dorsal root ganglia neurons.
- tdTomato expression correlated with TRPA1 activity in sensory afferents innervating the esophagus, gut, airways, bladder, and skin.
- Chemogenetic activation of TRPA1 nerves in the paw induced flinching behavior, confirming functional relevance.
- Limited TRPA1 expression was observed in non-neuronal cells, including subepithelial gut cells and cochlear supporting cells, but not in enterochromaffin cells or hair cells.
Conclusions:
- The developed TRPA1-FlpO mouse model is a valuable tool for mapping and manipulating TRPA1-expressing cells.
- This model facilitates the investigation of TRPA1's diverse roles in sensory pathways and other physiological systems.
- Further research using this model can elucidate TRPA1's involvement in various diseases and aid in the development of targeted therapies.
